GlaxoSmithKline : ViiV Healthcare announces analysis showing no antiretroviral therapy interruptions due to COVID-19 across its clinical development programme for investigational, long-acting cabotegravir and rilpivirine

For media and investors only

Issued: London, UK

Positive findings presented at IDWeek™ 2020 from a pooled analysis of six ongoing clinical trials in 16 countries showed 93% of participants maintained their injection visits in the midst of the COVID-19 pandemic with no instances of virologic failure or development of resistance

ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, today announced the positive findings of a pooled analysis of COVID-19-related impacts across the investigational long-acting cabotegravir and rilpivirine clinical development programme. In the midst of the global pandemic, the analysis found no antiretroviral therapy interruptions across the entirety of the ongoing clinical development programme for long-acting cabotegravir and rilpivirine. When missed visits occurred due to the pandemic, the analysis showed they were manageable and successfully mitigated primarily by switching patients onto short periods of daily oral therapy of cabotegravir and rilpivirine, with good tolerability and no virologic failure or emerging resistance. These findings were presented today at the 2020 Infectious Diseases Society of America (IDSA)IDWeek™.

Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare, said: 'The COVID-19 pandemic has presented us with perhaps the greatest real-world test to implementing the innovative regimen of long-acting cabotegravir and rilpivirine, which if approved, could shift the HIV treatment paradigm away from daily pills to injections administered by a healthcare provider every month or every two months. It's reassuring to know that even in the midst of a global pandemic that has led to restricted access to some clinics and providers, there were few injection visit interruptions and those that occurred were effectively managed by providing participants with oral treatment. These findings speak to how the regimen of cabotegravir and rilpivirine may be adapted to meet the needs of people living with HIV who have events in their lives that could cause them to miss an injection appointment.'

The pooled analysis examined 1,744 participants across 16 countries currently taking long-acting cabotegravir and rilpivirine as part of the regimen's ongoing global clinical development programme of six studies, which includes the phase IIb/IIIb LATTE-2, ATLAS, ATLAS-2M, FLAIR, POLAR, and CUSTOMIZE clinical trials. While the majority of participants (93%, 1,615) maintained their routine dosing schedule from December 2019 through the analysis end point of September 15, 2020, 129 participants (7%) in the ongoing clinical trials had a planned injection visit that was impacted by COVID-19.

To date, there have been no suspected or confirmed virologic failures observed for any participants whose planned injection visit schedules were impacted by COVID-19. Treatment interruption was prevented among impacted participants primarily by switching participants onto daily oral therapy with cabotegravir and rilpivirine (94 participants, 73%) or the daily oral standard of care antiretroviral therapy (27 participants, 21%). Seven participants (5%) were able to reschedule their long-acting injection visit. Of the participants who experienced an impact to their visit, 54 (42%) were due to clinic closure or staffing constraints, 11 (9%) were due to self-quarantine, 18 (14%) were due to confirmed or suspected COVID-19, and 46 (36%) were attributed to other reasons, including COVID-19-related travel restrictions.

One hundred ten of the 121 participants (91%) who transitioned to temporary oral therapy because of a COVID-impacted injection visit have since restarted therapy with long-acting cabotegravir and rilpivirine. Of those participants who transitioned back to injectables, the median duration of oral therapy was 51 days. Participants identified as impacted by COVID-19 will continue to be followed and data collected from that group is expected to be presented at a future medical meeting.

The long-acting regimen of cabotegravir and rilpivirine was approved by Health Canada in March 2020 and is currently under review by the US Food and Drug Administration and other global regulatory authorities. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency's (EMA) recently issued a positive opinionrecommending marketing authorisation for long-acting cabotegravir and rilpivirine in both injectable and tablet formulations. The CHMP positive opinion is one of the final steps before marketing authorisation is granted by the European Commission, which has the authority to approve medicines for use throughout the European Union.

About the long-acting regimen of cabotegravir and rilpivirine

The long-acting regimen of cabotegravir and rilpivirine is an investigational regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in patients who are virologically stable and suppressed (HIV-1 RNA less than 50 copies/mL). The complete regimen combines the integrase strand transfer inhibitor (INSTI) cabotegravir, developed by ViiV Healthcare, with rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) developed by Janssen Sciences Ireland UC, part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

INSTIs, like cabotegravir, inhibit HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection. Rilpivirine is an NNRTI that works by interfering with an enzyme called reverse transcriptase, which in turn stops the virus from multiplying.

CABENUVA (cabotegravir and rilpivirine extended release injectable suspensions) is currently only approved in Canada.

Important Safety Information for CABENUVA
Indications and clinical use:
CABENUVA (cabotegravir and rilpivirine extended release injectable suspensions) is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults to replace the current antiretroviral regimen in patients who are virologically stable and suppressed (HIV-1 RNA <50 copies/mL).

VOCABRIA (cabotegravir tablets) is indicated, in combination with EDURANT (rilpivirine tablets), as a complete regimen for short-term treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults who are virologically stable and suppressed (HIV-1 RNA <50 copies/mL) as: An oral lead-in to assess tolerability of cabotegravir prior to initiating CABENUVA.

Oral bridging therapy for missed CABENUVA injections

• Geriatrics (>65 years of age): Not sufficiently studied to determine if they respond differently than patients <65 years of age
• Pediatrics (<18 years of age): Safety and efficacy not established

Contraindications:

In combination with:

• Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, and phenytoin
• Antimycobacterials: Rifabutin, rifampin, rifapentine
• Glucocorticoid: Systemic dexamethasone (more than a single dose)
• St John's wort (Hypericum perforatum)

Relevant warnings and precautions:

• Should not be used in patients with known or suspected resistance to cabotegravir or rilpivirine
• Patients may still develop opportunistic infections and other complications of HIV infection
• Risk of transmission: precautions should be taken
• Depressive disorders
• Hepatotoxicity (serum transaminase elevations)
• Hepatic adverse events; increased risk for worsening or development of transaminase elevations in patients with hepatitis B or C co-infection or marked elevations in transaminases prior to treatment; monitoring of liver chemistries is recommended
• Loss of virologic response due to drug interactions; review concomitant medications during therapy
• Caution when used in combination with drugs that have a risk of Torsade de Pointes
• Skin and hypersensitivity reactions; discontinue immediately if signs or symptoms develop
• Administer the oral lead-in dosing prior to administration of CABENUVA to help identify patients who may be at risk of a hypersensitivity reaction
• Residual concentrations of cabotegravir and rilpivirine injections may remain in the systemic circulation of patients for up to 12 months or longer
• Risk of resistance due to treatment discontinuation
• Post-injection reactions within minutes after the injection of rilpivirine, including dyspnea, agitation, abdominal cramping, flushing, sweating, oral numbness, and changes in blood pressure. Reported in <0.5% of subjects and began to resolve minutes after the injection, and may have been associated with inadvertent (partial) IV administration
• Insufficient data in pregnant women; should not be used unless the potential benefits outweigh the potential risks
• HIV-1-infected mothers should not breastfeed their infants if receiving CABENUVA

For more information:

Please consult the Product Monograph at cabenuvapm.viivhealthcare.ca for additional important information relating to adverse reactions, drug interactions, and dosing. The Product Monograph is also available by calling 1-877-393-8448. To report an adverse event, please call 1-877-393-8448.

About ViiV Healthcare

ViiV Healthcare is a global specialist HIV company established in November 2009 by GlaxoSmithKline (LSE: GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances in treatment and care for people living with HIV and for people who are at risk of becoming infected with HIV. Shionogi joined in October 2012. The company's aim is to take a deeper and broader interest in HIV/AIDS than any company has done before and take a new approach to deliver effective and innovative medicines for HIV treatment and prevention, as well as support communities affected by HIV.

For more information on the company, its management, portfolio, pipeline and commitment, please visit www.viivhealthcare.com.

About GSK

GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com/about-us.

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Risk Factors' in the company's Annual Report on Form 20-F for 2019 and as set out in GSK's 'Principal risks and uncertainties' section of the Q2 Results and any impacts of the COVID-19 pandemic.